DescriptionThese targeted mutation mice exhibit a loss of both behavioral and molecular circadian rhythms. When placed in constant darkness, the mice undergo an immediate loss of circadian rhythmicity. Locomotor activity is impaired in both light and constant dark cycles.

Reduced total activity is seen as the mice age. They display a progressive noninflammatory arthropathy. Little pathology is seen prior to 11 weeks of age, but virtually all homozygotes develop joint ankylosis due to flowing ossification of ligaments and tendons by 35 weeks of age. Bone density and articular cartilage are unaffected.

Inactivation of the gene suppresses diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished in homozygotes, but the counterregulatory response of corticosterone and glucagon to insulin-induced hypoglycemia is retained.
Homozygotes are viable but not fertile and have an increased mortality rate after 26 weeks of age. A truncated, non-functional protein is produced. This strain may be useful in studies of circadian rhythm, arthritis, ankylosis, and glucose homeostasis.

DevelopmentThe helix-loop-helix domain within exon 4 and all of exon 5 were replaced with a neomycin resistance gene cassette. 129/Sv-derived GS1 embryonic stem (ES) cells were used to create the mutation. This line was backcrossed 14 times to C57BL/6 by the donating laboratory.

prolongation of the activated partial thrombosplastin time and a shortening of the prothrombin time by 1.6 seconds in 10 week old mice and 0.8 seconds in 30 week old mice, as well as increased plasma fibrinogen, factor VII and VIII levels indicate a hypercoagulable state that increases with age (MGI Ref ID J:191844)

numerous thrombi are seen in the venous sinus of penile sections from older males with priapism; thrombi contain platelets and fibrin and fibrin-rich laminar thrombus formation is seen extensively lining the endothelium (MGI Ref ID J:191844)

increase in the percentage of plasma factor VII at 30 weeks of age (MGI Ref ID J:191844)

increase in the percentage of plasma factor VIII at 10, but not 30, weeks of age (MGI Ref ID J:191844)

abnormal circulating fibrinogen level

increase in the level of plasma fibrinogen at 10 and 30 weeks of age (MGI Ref ID J:191844)

abnormal metabolism

at ZT10 in 40 week old mice, the accumulation of reactive oxygen species is increased in the kidney, heart and spleen but decreased in the liver relative to time and age matched controls (MGI Ref ID J:110697)

increase in reactive oxygen species accumulation is age and tissue dependent (MGI Ref ID J:110697)

abnormal nitric oxide homeostasis

basal nitric oxide release is attenuated in the thoracic aorta at 30 weeks of age (MGI Ref ID J:191844)

mutants develop spontaneous priapism that increases with age, from 0% at 10 weeks to 8% at 20-25 weeks, and 60% at 25-30 weeks, which is not seen in wild-type mice at any age (MGI Ref ID J:191844)

numerous thrombi are seen in the venous sinus of penile sections; thrombi contain platelets and fibrin and fibrin-rich laminar thrombus formation is seen extensively lining the endothelium (MGI Ref ID J:191844)

small seminal vesicle

detectable by 10 weeks of age and becoming more pronounced with age (MGI Ref ID J:110697)

at 10 and 40 weeks of age no differences are detected in the numbers of red blood cells or platelets (MGI Ref ID J:110697)

abnormal leukocyte tethering or rolling

despite an increase in leukocytes, lower numbers of rolling leukocytes over endothelium when activated with A23187 are seen in mutants compared to wild-type at both 10 and 30 weeks of age (MGI Ref ID J:191844)

decreased leukocyte cell number

decrease in the number of white blood cells at 40 weeks of age compared to age matched controls (MGI Ref ID J:110697)

however, ultradian rhythms are maintained and are stronger than any residual circadian rhythms (MGI Ref ID J:125921)

the diurnal variation in restraint induced changes in blood pressure is abolished and the stress induced alteration in blood pressure is lower at ZT12 (MGI Ref ID J:125921)

abnormal vascular smooth muscle physiology

endothelium-dependent vasomotor responses are altered, with an increase of phenylephrine contraction induced by NOS inhibitors and suppression of acetylcholine-muscarinic receptor-induced endothelium-dependent relaxations in aortic rings of mutants, particularly at 30 weeks of age (MGI Ref ID J:191844)

endothelium-dependent vasomotor responses are altered, with an increase of phenylephrine contraction induced by NOS inhibitors and suppression of acetylcholine-muscarinic receptor-induced endothelium-dependent relaxations in aortic rings of mutants, particularly at 30 weeks of age (MGI Ref ID J:191844)

increase in the level of plasma fibrinogen at 10 and 30 weeks of age (MGI Ref ID J:191844)

abnormal leukocyte tethering or rolling

despite an increase in leukocytes, lower numbers of rolling leukocytes over endothelium when activated with A23187 are seen in mutants compared to wild-type at both 10 and 30 weeks of age (MGI Ref ID J:191844)

decreased leukocyte cell number

decrease in the number of white blood cells at 40 weeks of age compared to age matched controls (MGI Ref ID J:110697)

at 30 weeks of age hair regrowth after shaving is delayed with only 1 of 5 mice showing partial regrowth after 3 months (MGI Ref ID J:110697)

however, at 10 weeks of age hair regrowth is normal (MGI Ref ID J:110697)

cellular phenotype

abnormal leukocyte tethering or rolling

despite an increase in leukocytes, lower numbers of rolling leukocytes over endothelium when activated with A23187 are seen in mutants compared to wild-type at both 10 and 30 weeks of age (MGI Ref ID J:191844)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

most wounds consist mainly of an inflammatory fibrin clot with hardly any fibroblast or keratinocyte proliferation (MGI Ref ID J:193286)

decreased circulating progesterone level

levels are lower compared to controls regardless of the time of day on day 3 to day 4 of gestation (MGI Ref ID J:151819)

behavior/neurological phenotype

abnormal circadian phase

when a 6 hour light pulse is administered 22 days after placement in constant darkness, no effect on locomotor behavior in null mice is observed nor are there phase shifts or suppression of activity, whereas wild-type mice show a ~3.5 hour phase delay after a light pulse (MGI Ref ID J:66502)

few null mutants begin activity within 0.5 hours of lights-off, and 2/17 do not become active at all, whereas all wild-type and heterozygous mice begin activity within 0.5 hours (MGI Ref ID J:66502)

28% of wheel-running activity of mutants is during the light phase, in contrast to 4.2 or 4.1% during light phase in wild-type or heterozygous mice (MGI Ref ID J:66502)

abnormal locomotor activation

level of wheel-running activity in mutants is >3-fold lower during a light cycle and in constant darkness relative to wild-type mice (MGI Ref ID J:66502)

arrhythmic circadian persistence

when placed in constant darkness after entrainment to a 12 hour/12 hour light/dark schedule, homozygotes do not express any circadian rhythm or locomotor activity in constant darkness (MGI Ref ID J:66502)

transfer of null cells into wild-type mice rescues B cell development and wild-type cells transferred into null mice show a partial block in development suggesting an alteration in the bone marrow microenvironment (MGI Ref ID J:118522)

abnormal T cell subpopulation ratio

the percentage of CD4+ T cells is slightly increased in the blood and spleen (MGI Ref ID J:118522)

however, the total number of CD4+ cells is not changed (MGI Ref ID J:118522)

transfer of null cells into wild-type mice rescues B cell development and wild-type cells transferred into null mice show a partial block in development suggesting an alteration in the bone marrow microenvironment (MGI Ref ID J:118522)

abnormal T cell subpopulation ratio

the percentage of CD4+ T cells is slightly increased in the blood and spleen (MGI Ref ID J:118522)

however, the total number of CD4+ cells is not changed (MGI Ref ID J:118522)

islets show up to a 60% reduction in insulin secretion in response to glucose, KCI, exendin 4, forskolin and 8-bromo-cAMP (MGI Ref ID J:162641)

decreased pancreatic islet number

2-fold reduction in the percentage of large islets (MGI Ref ID J:162641)

Arntltm1Bra/Arntltm1Bra

involves: 129/Sv * C57BL/6 * C57BL/6J

integument phenotype

abnormal hair cycle

mice exhibit a delay in the first synchronized anagen that persists through out the hair cycle (MGI Ref ID J:151782)

however, the duration of the hair cycle is normal (MGI Ref ID J:151782)

abnormal hair cycle anagen phase

the first synchronized anagen is delayed compared to in wild-type mice (MGI Ref ID J:151782)

abnormal hair follicle matrix region morphology

hair follicles of mutant mice contain a thickened keratinocyte strand between the dermal papilla and the club hair but lack the highly proliferative matrix required for downward growth of the hair follicle during anagen (MGI Ref ID J:151782)

A portion of exon 4 containing the helix-loop-helix coding domain and all of exon 5 were replaced by a neomycin selection cassette. A larger transcript, resulting from a cryptic splice site between exon 3 and the neomycin resistance gene, was detected byNorthern blot analysis. The polypeptide truncates 15 residues after this splice site, prior to the functional domains encoded by exon 4 in the wild-type locus. [MGI Ref ID J:66502]

Health & Colony Maintenance Information

Animal Health Reports

Colony Maintenance

Breeding & Husbandry

When maintained as a live colony, hetetozygotes may be bred. It is recommended that females be disturbed as little as possible because they are prone to killing their litters. Homozygotes are viable, but both males and females are reportedly sterile.

Standard Supply

Repository-Live.Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations

Live Mice

Price per mouse (US dollars $)

Gender

Genotypes Provided

Individual Mouse

$310.70

Female or Male

Heterozygous for Arntltm1Bra

Price per Pair (US dollars $)

Pair Genotype

$404.30

Heterozygous for Arntltm1Bra x Wild-type for Arntltm1Bra

$404.30

Wild-type for Arntltm1Bra x Heterozygous for Arntltm1Bra

Standard Supply

Repository-Live.Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Standard Supply

Repository-Live.Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering InformationJAX® MiceSurgical and Preconditioning ServicesJAX® ServicesCustomer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150 Technical Support Email Form

Terms of Use

Contact information

Contracts Administration

phone:

207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.